Human alpha-aminoadipic semialdehyde synthase (AASS); A Target Enabling Package

This work provides the early tools to develop substrate reduction inhibitors for a genetic childhood seizure disorder, with the hypothesis to target the enzyme (AASS) upstream of the defective gene (ALDH7A1) in the human lysine metabolic pathway. This TEP package includes recombinant human AASS purification protocols, structures of the AASS second domain in different states, in vitro assays to detect ligand binding (differential scanning fluorimetry) and enzyme activity (NADH formation) of human AASS, as well as initial chemical matters.

本研究提供了用于开发儿童遗传性癫痫发作障碍底物还原抑制剂的早期工具，其研究假说为靶向人类赖氨酸代谢通路中缺陷基因（ALDH7A1）上游的酶（AASS）。本TEP套件包含重组人AASS的纯化方案、不同状态下AASS第二结构域的结构、用于检测人AASS配体结合（差示扫描荧光法）与酶活性（以烟酰胺腺嘌呤二核苷酸还原型[NADH]生成为检测指标）的体外实验方法，以及初始化学试剂。